Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation...

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Published inNPJ precision oncology Vol. 8; no. 1; pp. 27 - 13
Main Authors Yousef, Abdelrahman, Yousef, Mahmoud, Chowdhury, Saikat, Abdilleh, Kawther, Knafl, Mark, Edelkamp, Paul, Alfaro-Munoz, Kristin, Chacko, Ray, Peterson, Jennifer, Smaglo, Brandon G., Wolff, Robert A., Pant, Shubham, Lee, Michael S., Willis, Jason, Overman, Michael, Doss, Sudheer, Matrisian, Lynn, Hurd, Mark W., Snyder, Rebecca, Katz, Matthew H. G., Wang, Huamin, Maitra, Anirban, Shen, John Paul, Zhao, Dan
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 03.02.2024
Nature Publishing Group
Nature Portfolio
Subjects
692/308/409
692/4028/67/1504/1713
Cancer Research
Clinical outcomes
Gene Therapy
Human Genetics
Internal Medicine
Medical prognosis
Medicine
Medicine & Public Health
Metastasis
Mutation
Oncology
Pancreatic cancer
Tumors
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Summary:The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic ( p  < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2–3.0, p  = 0.006] and 22 months [HR: 1.7, 95% CI 1.3–2.3, p  < 0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2–2.4, p  = 0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05–2.99, p  = 0.04). Similar findings were observed in the external validation cohort (PanCAN’s Know Your Tumor® dataset, n  = 408).
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ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-024-00505-0